The proposed studies have as their rationale the findngs of clinical and epidemiological teratology that (1) the neural-tube nonclosure defects anencephaly and spina bifida frequently occur together in individuals and families; and (2) spina bifida is usually accompanied by hydrocephalus and certain cerebellar abnormalities. In attempts to understand the nature of these relationships, two types of studies will be made. The first will test the hypothesis that embryos destined by heredity to develop exencephaly have a reduced threshold for the development of spina bifida, and vice versa. This will be done by exposing mouse embryos of stocks containing mutant genes producing one or the other of these conditions to teratogenic agents capable of inducing the other one, to determine whether embryos with a hereditary defect are more prone to the production of the induced defect than their normal littermates. In the second type of study, embryos and fetuses of sequential ages with the gene-caused spina bifida and their normal littermates will be histologically examined and analyzed to detect the presence of features of the brain that may prognose the occurrence of hyrocephalus and cerebellar aberrations.